The South African AIDS Vaccine Initiative (SAAVI) commemorated the launch of the South African arm of a Phase I AIDS vaccine trial at the Emavundleni Prevention Centre in Cape Town on July 20. The purpose of the trial is to evaluate the safety and immunogenicity of two vaccine candidates, developed by researchers in South Africa, which are administered sequentially in a prime-boost regimen.

The trial, known as SAAVI102/HVTN 073, is being conducted in collaboration with the HIV Vaccine Trials Network (HVTN) and the National Institute of Allergy and Infectious Diseases (NIAID), part of the US National Institutes of Health (NIH).

Researchers plan to enroll 36 volunteers at two clinical research centers in South Africa—the Emavundleni Centre in Cape Town and Chris Hani Baragwanath Hospital in Soweto. Twelve volunteers have already been successfully enrolled and vaccinated in the US arm of the study, which is being conducted at the Fenway Community Health Center in Boston.

The prime-boost regimen being tested is comprised of a DNA vaccine candidate followed by a modified vaccinia Ankara (MVA) vector-based candidate, both of which are modified by researchers to carry fragments of clade C HIV, the subtype that is predominant in South Africa, to induce an immune response against HIV. Both candidates were tested in the laboratory and in animal models prior to this study and neither can cause HIV infection.

The launch of the South African arm of the study was significant because the prime-boost regimen was developed by researchers in the country. “We’re seen as the place to test vaccines, now we’ve developed one,” said Anna-Lise Williamson of the University of Cape Town, who led the development of the vaccine candidates. “It usually happens the other way around.”

The DNA vaccine candidate was constructed in South Africa using a plasmid provided by the Vaccine Research Center at NIAID. The MVA candidate was developed by researchers at the University of Cape Town with funding from SAAVI and the NIH. Both candidates were manufactured in the US. SAAVI is the lead program of the South African Medical Research Council (MRC) and was established by the South African government and the energy supply company Eskom in 1999 to coordinate the development of an HIV vaccine for southern Africa.

Anthony Mbewu, president of the MRC, called the launch of this trial a “scientific milestone,” which he said “ensures that South Africa will be better able to design and develop vaccines against infectious agents in the future.”

Anthony Fauci, director of NIAID, said that scientists in South Africa received more NIAID funding last year than any other country outside the US. “You have the intellectual capital and people who are passionate about health, especially in the arena of HIV/AIDS,” he said. Fauci also discussed the “extensive challenges” facing AIDS vaccine researchers.

Despite these challenges, many speakers noted the importance of continuing AIDS vaccine research. “The cost of [HIV] treatment is very high,” said Naledi Pandor, the South African Minister of Science and Technology. “I therefore cannot overstate the importance of the development of a vaccine for the South African population.”

What can researchers learn from studying communities in preparation for AIDS vaccine clinical trials?

Volunteers are an essential component of AIDS vaccine clinical trials. Without the many individuals who are willing to participate in clinical studies, researchers would not be able to test candidate vaccines and determine if they are safe and effective. Recruiting thousands of volunteers for large Phase III efficacy trials is a daunting task. One way to effectively reach and engage potential volunteers for clinical trials is to gain a better understanding of the communities in which trials will take place. This is sometimes accomplished by conducting social science research.

Social science research, as its name implies, involves the study of human behavior and relationships. While more subjective than virology or immunology, social science research can include behavioral, health policy, and health systems research, as well as social epidemiology.

Social scientists have been studying HIV since the beginning of the epidemic. HIV is most often transmitted through sexual activity or injection drug use, and so developing a better understanding of the societal impact and drivers of the pandemic has been crucial to understanding HIV, particularly with regard to prevention. Social science research can also be used to collect information that can help ensure that AIDS vaccine clinical trials are conducted successfully.

Supporting volunteer recruitment and retention

If a trial is designed to show whether a particular candidate vaccine is effective at preventing HIV infection, individuals who participate in the trial must be at risk of HIV infection through natural exposure to the virus (see VAX May 2008Primer on Understanding the Recruitment of Volunteers at Risk of HIV Infection). Importantly, volunteers in a vaccine trial are never purposely exposed to HIV and the vaccine candidates cannot cause HIV infection.

To ensure that at-risk volunteers are included, clinical trials are often conducted in areas where the rate of new HIV infections or incidence is highest. It is also in these areas or specific populations—such as men who have sex with men (MSM) or commercial sex workers—that a vaccine is needed most and would ultimately offer the greatest benefit, and so it is therefore important that these individuals are part of the clinical process.

Social scientists have employed in-depth interviews, focus groups, and anonymous surveys to gain information about these at-risk populations. To make sure the tools being used to collect the data—such as a questionnaire—are scientifically rigorous enough, social scientists will sometimes use independent auditors to review the language in the questionnaire and the method and settings in which the questions are asked.

The information collected from these surveys or interviews helps researchers identify factors that may impede recruitment, enrollment, and retention of at-risk individuals in clinical studies. There are different factors within these populations that affect a person’s vulnerability with regard to HIV, and understanding these factors can help make the recruitment and enrollment process for clinical trials run more smoothly.

Several groups involved in AIDS vaccine research and development are currently engaged in social science research, including IAVI, the Kenya AIDS Vaccine Initiative, the Uganda Virus Research Institute, the Desmond Tutu HIV Foundation, the Aurum Institute, and the US National Institute of Allergy and Infectious Diseases, as well as many others. This research is helping to determine, for example, if certain populations are suitable for upcoming vaccine trials. Other research is focused on identifying barriers and opportunities for involving MSM or transgendered communities in HIV prevention research.

Gender issues

One particularly important avenue of social science research has focused on the role of gender in the HIV pandemic, and in AIDS vaccine research and development more specifically. Biological distinctions between men and women may impact the efficacy of a vaccine. Also, because HIV prevalence is so high among women, particularly in southern Africa, it is important that AIDS vaccine candidates be tested in adequate numbers of female volunteers (see VAXMarch 2008 Primer on Understanding the Recruitment and Retention of Women in Clinical Trials).

Social science research can help assess the barriers that discourage women in developing countries from participating in clinical trials. This knowledge can enable researchers to develop strategies that are aimed specifically at enrolling women. For instance, in a Kenyan study conducted by IAVI and the International Center for Research on Women, social scientists discovered that women were more vulnerable to HIV stigma than men, which may have affected their willingness to participate in a clinical trial. The study found that while men and women were both concerned that participating in a trial could potentially damage their personal relationships, the concern loomed larger for women, who are more likely to be dependent on a relationship for economic reasons.

By building a better understanding about the fears women and men have about clinical trials and HIV/AIDS and how their decision making processes may differ, researchers can hopefully strengthen outreach, recruitment, retention, and support systems within the context of AIDS vaccine clinical trials.